Gene-Based Single Nucleotide Polymorphisms and Linkage Disequilibrium Patterns of 29 Asthma Candidate Genes in the Chromosome 5q31–33 Region in Koreans

2006 ◽  
Vol 139 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Ha-Jung Ryu ◽  
Ho-Youl Jung ◽  
Jung-Sun Park ◽  
Gil-Mi Ryu ◽  
Jee Yeon Heo ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Candidate Genes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Chromosome 5Q31

Association of Single Nucleotide Polymorphisms in Klotho with Priapism in Sickle Cell Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1673-1673
Author(s):  
Vikki G. Nolan ◽  
Clinton Baldwin ◽  
Qianli Ma ◽  
Diego F. Wyszynski ◽  
John J. Farrell ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Candidate Genes ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Likelihood Method ◽  
P Value ◽  
Nucleotide Polymorphisms ◽  
Genetic Modifiers ◽  
Single Nucleotide

Abstract The phenotypic heterogeneity of sickle cell anemia (HbSS) is likely to be accounted for by multiple genetic modifiers. Priapism, a common vasoocclusive complication of HbSS, may reflect sickle vasculopathy. We hypothesized that the likelihood of developing priapism, and other vascular complications of sickle cell disease, may be influenced by genetic heterogeneity in genes that modulate inflammation, oxidant injury, nitric oxide (NO) biology, vasoregulation, cell-cell interaction and hemostasis. Accordingly, we studied patients with HbSS with or without coincident α thalassemia and examined the association of 129 single nucleotide polymorphisms (SNPs) in 44 candidate genes with priapism. One hundred forty-eight patients had at least one episode of priapism and were compared with 529 controls. Validated SNPs in the candidate genes were first selected from a public database. Genotypic counts were compared between cases and controls using multiple logistic regression. For each SNP, odds ratio (OR) and 95% confidence intervals (CI) were calculated. Pairwise linkage disequilibrium between each pair of SNP loci was evaluated by using a maximum likelihood method to infer phase for dual heterozygotes and was expressed as r2. In our first analysis, we considered a SNP to have an association with a phenotype when the p-value was equal to or less than 0.01, unless there was more than one SNP in a gene showing an association, when the p-value for significance was set at 0.05. When a SNP met these criteria, we further studied the gene with as many informative SNPs as possible. Haplotypes were reconstructed by using Bayesian methods as implemented in the PHASE package. A sliding window approach was used to assess evidence for association between haplotype and priapism. Patients with HbSS-α thalassemia were less likely to have priapism than patients with HbSS (p<0.05). Two SNPs in Klotho gene (KL), rs657049 and rs211239, were associated with priapism by genotypic analysis (OR: 1.74, 95% CI 1.03–2.96 and OR: 1.74, 95% CI: 1.16–2.63, respectively). Since it is likely that the control group contains patients who might ultimately develop priapism, this may be an underestimate of the true association. Seventeen SNPs were used to reconstruct the haplotype of KL gene for cases and controls separately. Haplotype association analysis was performed using sliding windows of 2, 3, and 4 SNPs separately, and p-values were calculated after 10,000 permutations. We found that haplotypes around rs211239 (5th SNP among 17 SNPs by physical location) were associated with priapism in different windows, (1) 2 SNPs: window 3-4 and 4-5, p: 0.001 and 0.01 respectively, (2) 3 SNPs: window 2-3-4, 4-5-6 and 6-7-8, p: 0.004, 0.01, and 0.05, respectively, (3) 4 SNPs: window 1-2-3-4, 3-4-5-6, and 4-5-6-7, p: 0.03, 0.002, 0.02, respectively. KL encodes a membrane protein that regulates many vascular functions, including endothelial NO release and a variant protein may alter NO biology. We conclude that polymorphisms in a limited number of genes, or in linkage disequilibrium with functionally important genes, may set an overall risk for some vasoocclusive complications of HbSS. Identifying potential genetic modifiers, like KL, will permit these genes to be evaluated in biological studies and for networks of genotype-phenotype interactions to be modeled.

Protein Variation in ADH and ADH-RELATED in Drosophila pseudoobscura: Linkage Disequilibrium Between Single Nucleotide Polymorphisms and Protein Alleles

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 673-687
Author(s):  
Stephen W Schaeffer ◽  
C Scott Walthour ◽  
Donna M Toleno ◽  
Anna T Olek ◽  
Ellen L Miller
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Drosophila Pseudoobscura ◽  
Linkage Disequilibrium Mapping ◽  
Nucleotide Polymorphisms ◽  
Neutral Model ◽  
Significant Linkage Disequilibrium ◽  
Single Nucleotide ◽  
Synonymous Sites ◽  
Significant Linkage

Abstract A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

The effect of linkage disequilibrium on the estimates of Single Nucleotide Polymorphic effects

2009 ◽  
Vol 2009 ◽  
pp. 44-44
Author(s):  
K Moore ◽  
J Gibson ◽  
D Johnston
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Improvement ◽  
Dairy Herd ◽  
Physical Distance ◽  
Causative Mutation ◽  
Nucleotide Polymorphisms ◽  
Production Traits ◽  
Single Nucleotide Polymorphic ◽  
Single Nucleotide

The identification and exploitation of single nucleotide polymorphisms (SNP) associated with production traits present new opportunities for livestock genetic improvement. Often the identified SNP is not the causative mutation but rather is in some degree of linkage disequilibrium (LD). LD markers within 5cM can be considered as direct markers for the causative mutation because they are located close to the causative mutation (Dekkers, 2004). In a dairy herd, Farnir et al., (2000) estimated that the average LD, measured as D′ was 0.5 for loci pairs positioned within 5cM. Goddard et al., (2006) estimated that LD measured as r2 decreased rapidly as the physical distance between loci increased; at a separating distance of 0.5Mb the LD (r2) was only approximately 0.2. The aim of this work was to use stochastic simulation to investigate the effect that the distance between the SNP and causative mutation had on the accuracy of estimating additive and dominance effects of the causative mutation.

Association studies of multiple candidate genes for Parkinson's Disease using single nucleotide polymorphisms

2002 ◽  
Vol 51 (4) ◽  
pp. 534-534 ◽  
Author(s):  
Yoshio Momose ◽  
Miho Murata ◽  
Kazuhiro Kobayashi ◽  
Masaji Tachikawa ◽  
Yuko Nakabayashi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Nucleotide Polymorphisms ◽  
Candidate Genes ◽  
Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide
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